Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK real-world experience.

ABSTRACT: Bendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicenter observational study evaluating bendamustine toxicity in real-world practice. Patients receiving at least 1 dose of bendamustine with/without rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details, and grade 3 to 5 adverse events (AEs) were analyzed and correlated. In total, 323 patients were enrolled from 9 National Health Service hospitals. Most patients (96%) received bendamustine-R, and 46%, R maintenance. Overall, 21.7% experienced serious AEs (SAE) related to treatment, including infections in 12%, with absolute risk highest during induction (63%), maintenance (20%), and follow-up (17%) and the relative risk highest during maintenance (54%), induction (34%), and follow-up (28%). Toxicity led to permanent treatment discontinuation for 13% of patients, and 2.8% died of bendamustine-related infections (n = 5), myelodysplastic syndrome (n = 3), and cardiac disease (n = 1). More SAEs per patient were reported in patients with mantle cell lymphoma, poor preinduction performance status (PS), poor premaintenance PS, and abnormal preinduction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3 of 10 opportunistic infections occurred despite prophylaxis. In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to those of trial populations of younger, fitter patients. Poor PS, mantle cell histology, and maintenance R were potential risk factors. Infections, including late onset events, were the most common treatment-related SAE and cause of death, warranting extended antimicrobial prophylaxis and infectious surveillance, especially for maintenance-treated patients.

Pilot study of lung cancer screening for survivors of Hodgkin lymphoma.

Hodgkin lymphoma (HL) treatment increases the risk of lung cancer. Most HL survivors are not eligible for lung cancer screening (LCS) programmes developed for the general population, and the utility of these programmes has not been tested in HL survivors. We ran a LCS pilot in HL survivors to describe screening uptake, participant characteristics, impact of a decision aid and screen findings. HL survivors treated ≥5 years ago with mustine/procarbazine and/or thoracic radiation, were identified from a follow-up database and invited to participate. Participants underwent a low-dose CT (LDCT) reported using protocols validated for the general population. Two hundred and eighteen individuals were invited, 123 were eligible, 102 were screened (58% response rate): 58% female, median age 52 years, median 22 years since HL treatment. 91.4% were deemed to have made an informed decision; participation was not influenced by age, gender, years since treatment or deprivation. Only 3/35 ever-smokers met criteria for LCS through the programme aimed at the general population. Baseline LDCT results were: 90 (88.2%) negative, 10 (9.8%) indeterminate, 2 (2.0%) positive. Two 3-month surveillance scans were positive. Of 4 positive scans, 2 patients were diagnosed with small-cell lung cancer; 1 underwent curative surgery. Coronary artery calcification was detected in 36.3%, and clinically significant incidental findings in 2.9%. LDCT protocols validated in ever-smokers can detect asymptomatic early-stage lung cancers in HL survivors. This finding, together with screening uptake and low false positive rates, supports further research to implement LCS for HL survivors.

Likely uptake of a future a lung cancer screening programme in Hodgkin lymphoma survivors: a questionnaire study.

BACKGROUND: Many Hodgkin lymphoma (HL) survivors are at increased risk of subsequent malignant neoplasms (SMN), including lung cancer, due to previous treatment for HL. Lung cancer screening (LCS) detects early-stage lung cancers in ever smokers but HL survivors without a heavy smoking history are ineligible for screening. There is a rationale to develop a targeted LCS. The aim of this study was to investigate levels of willingness to undergo LCS in HL survivors, and to identify the psycho-social factors associated with screening hesitancy. METHODS: A postal questionnaire was sent to 281 HL survivors registered in a long-term follow-up database and at increased risk of SMNs. Demographic, lung cancer risk factors, psycho-social and LCS belief variables were measured. Multivariable logistic regression analysis was performed to determine the factors associated with lung cancer screening hesitancy, defined as those who would 'probably' or 'probably not' participate. RESULTS: The response rate to the questionnaire was 58% (n = 165). Participants were more likely to be female, older and living in a less deprived area than non-participants. Uptake (at any time) of breast and bowel cancer screening among those previously invited was 99% and 77% respectively. 159 participants were at excess risk of lung cancer. The following results refer to these 159. Around half perceived themselves to be at greater risk of lung cancer than their peers. Only 6% were eligible for lung cancer screening pilots aimed at ever smokers in the UK. 98% indicated they would probably or definitely participate in LCS were it available. Psycho-social variables associated with LCS hesitancy on multivariable analysis were male gender (OR 5.94 CI 1.64-21.44, p < 0.01), living in an area with a high index of multiple deprivation decile (deciles 6-10) (OR 8.22 CI 1.59-42.58, p < 0.05) and lower levels of self-efficacy (OR 1.64 CI 1.30-2.08 p < 0.01). CONCLUSION: HL survivors responding to this survey were willing to participate in a future LCS programme but there was some hesitancy. A future LCS trial for HL survivors should consider the factors associated with screening hesitancy in order to minimise barriers to participation.

The development of a decision aid to support Hodgkin lymphoma survivors considering lung cancer screening.

BACKGROUND: Decisions aids (DA) can support patients to make informed decisions about screening tests. This study describes the development and initial evaluation of a lung cancer screening (LCS) DA targeted towards survivors of Hodgkin lymphoma (HL). METHODS: A prototype decision aid booklet was developed and subsequently reviewed by a steering group who provided feedback. Revisions were made to produce the DA tested in this study. HL survivors were recruited to an online survey and/or focus groups. Lymphoma practitioners were invited to an interview study. In the online survey, decisional conflict scales and knowledge scales were completed before and after accessing the DA. The focus groups and interviews explored acceptability and comprehensibility and the decisional needs of stakeholders. Focus groups and interviews were audio recorded. The framework method was used to analyse qualitative data. RESULTS: 38 HL survivors completed the online survey. Following exposure to the DA, knowledge of LCS and risk factors and decisional conflict scores (total score and subscale scores) improved significantly. 11 HL survivors took part in two focus groups (n = 5 and n = 6) and 11 practitioners were interviewed. Focus group and interview results: The language, format and length were considered acceptable. Both groups felt the DA was balanced and presented a choice. Icon arrays were felt to aid comprehension of absolute risk values and for some survivors, they reduced affective risk perceptions. Among survivors, the impact of radiation risk on decision making varied according to gender and screening interval, whilst practitioners did not anticipate it to be a major concern for patients. Both groups expressed that a screening offer could mitigate anxiety about lung cancer risk. As anticipated by practitioners, survivors expressed a desire to seek advice from their clinical team. Practitioners thought the DA would meet their informational needs regarding LCS  when supporting survivors. CONCLUSIONS: The DA is considered acceptable by HL survivors and practitioners. The DA reduces decisional conflict and improves knowledge in HL survivors, suggesting that it would support HL survivors to make informed decisions when considering LCS in a future clinical trial.

The perspectives of survivors of Hodgkin lymphoma on lung cancer screening: A qualitative study.

BACKGROUND: Hodgkin lymphoma survivors (HLS) are at excess risk of lung cancer as a consequence of HL treatment. HLS without a heavy smoking history are currently unable to access lung cancer screening (LCS) programmes aimed at ever smokers, and there is an unmet need to develop a targeted LCS programme. In this study we prospectively explored HLS perspectives on a future LCS programme, including motivating factors and potential barriers to participation, with the aim of identifying ways to optimise uptake in a future programme. METHODS: Semistructured telephone interviews were conducted with HLS, aged 18-80 and lymphoma-free for ≥5 years, selected from a clinical database (ADAPT). Participants provided informed consent. Data were analysed using inductive thematic analysis. RESULTS: Despite awareness of other late effects, most participants were unaware of their excess risk of lung cancer. Most were willing to participate in a future LCS programme, citing the potential curability of early-stage lung cancer and reassurance as motivating factors, whilst prior experience of healthcare was a facilitator. Whilst the screening test (a low dose CT scan) was considered acceptable, radiation risk was a concern for some and travel and time off work were potential barriers to participation. CONCLUSIONS: Our results suggest that most HLS would participate in a future LCS programme, motivated by perceived benefits. Their feedback identified a need to develop educational materials addressing lung cancer risk and concerns about screening, including radiation risk. Such materials could be provided upon an invitation to LCS. Uptake in a future programme may be further optimized by offering flexible screening appointments close to home.

Prognostic factors for relapse in resected gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis.

BACKGROUND: Gastroenteropancreatic neoplasms (GEP-NENs)can potentially be cured through surgical resection, but only 42-57% achieve 5-year disease-free survival.There is a lack of consensus regarding the factorsassociated withrelapse followingresection ofGEP-NENs. METHODS: Asystematic review identified studies reporting factors associated with relapse in patients with GEP-NENs following resection of a primary tumour. Meta-analysis was performed to identify the factors prognostic for relapse-free survival (RFS)oroverall survival (OS). RESULTS: 63 studies comprising 13,715 patients were included; 56 studies reported on pancreatic NENs (12,418 patients), 24 reported on patients with grade 1-2 tumours (4,735 patients). Median follow-up was 44.2 months, median RFS was 32 months. Pooling of multivariable analyses of GEP-NENs (all sites and grades) found the following factors predicted worse RFS (all p values < 0.05): vascular resection performed, metastatic disease resected, grade 2 disease, grade 3 disease, tumour size > 20 mm, R1 resection, microvascular invasion, perineural invasion, Ki-67 > 5% and any lymph node positivity. In a subgroup of studies comprising exclusively of grade 1-2 GEP-NENs, R1 resection, perineural invasion, grade 2 disease, any lymph node positivity and tumour size > 20 mm predicted worse RFS (all p values < 0.05). Few OSdata were available for pooling; in univariableanalysis(entire cohort), grade 2 predicted worse OS (p = 0.007), whileR1 resectiondid not (p = 0.14). CONCLUSIONS: The factors prognostic for worse RFS following resection of a GEP-NEN identified in this meta-analysis could be included in post-curative treatment surveillance clinical guidelines and inform the stratification and inclusion criteria of future adjuvant trials.

Nurses and heart failure education in medical wards.

Heart failure is a chronic debilitating disease with significant hospitalisation rates. Information and education are foundational elements in making the lifestyle changes required for effective self-management of the symptoms of heart failure. This paper reports a study of medical nurses' education activities with heart failure patients in terms of the topics they addressed and the educational resources they found most useful. A random sample of 540 medical ward nurses were surveyed in 2009 using a postal questionnaire. The response rate was 47% (234 medical ward nurses who cared for patients with heart failure). Quantitative data were analysed using descriptive statistics, qualitative data through a content analysis approach. The majority of respondents (66.7%) cared for patients with heart failure several times each week. The total time spent on educational activities by most respondents (70.6%) was estimated as 20 minutes or less over the hospitalisation. Printed material was the most commonly used education resource although 35 respondents also referred to online information and 84 nurses did not use educational material at all. The most frequent education topics discussed were medication, signs and symptoms and general information about heart failure. Psychological factors and prognosis information were the topics least discussed with patients. Respondent suggestions to improve patient access to heart failure information included more printed information in wards such as pamphlets in various languages, information about useful websites and having key resources available in te reo Maori. The heart failure educator was identified as an important resource for both nurses and patients. The study highlighted the limited time many respondents spent on educational activities and the need for readily available educational resources to optimise patient heart failure education opportunities.

Nurses' use of online health information in medical wards.

AIM: This paper is a report of a study of nurses' access, use and evaluation of online health information in medical wards. BACKGROUND: Online health information is commonly used by patients with chronic illness to support their education needs. Nurses have a critical role in assisting patients to access and use this information. METHOD: This descriptive cross-sectional survey of a random sample of 540 nurses employed in medical wards was carried out in 2009. The response rate was 58·7% (293). The analytical approach included descriptive statistics and non-parametric tests of correlation and differences between groups. A content analysis was performed on the qualitative data. RESULTS: Most respondents (78·6%) were satisfied with work Internet access and 58·2% believed that the use of online information improved care delivery. Nearly half the group was aware of patient misconceptions about their illness due to incorrect interpretations of online information, but only 24·4% checked if patients used online information. There was a significant association between assessing patients use and awareness of patient misconceptions. CONCLUSION: The findings of this study highlight that while online resources add to education opportunities, the ongoing nursing assessment required to determine online information needs is not always incorporated into nursing practice. Patient misunderstandings of online material were also identified; developing patient competency in evaluating open access health information should now be recognized as an integral aspect of illness management education.